A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients （FRESCO) (FRESCO)

A Randomized, Double-blind and Placebo-controlled Phase III Trial Comparing Fruquintinib Efficacy and Safety vs Best Support Care (BSC) in Advanced Colorectal Cancer Patients Who Have Failed at Least Second Lines of Chemotherapies

Fruquintinib administered at 5mg once daily(QD) in 4 weeks treatment cycle (three weeks on and one week off) was well tolerated and demonstrated encouraging preliminary clinical antitumor activity in patients with metastatic colorectal cancer (CRC) in phase Ib and phase 2 study. This study is aimed to evaluate the efficacy and safety of Fruquintinib in the treatment of patients with metastatic CRC who have progressed after second line or above standard chemotherapy

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fruquintinib; Drug: placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial to compare the efficacy and safety of Fruquintinib plus BSC versus placebo plus BSC in patients with metastatic colorectal cancer who have progressed after second-line or above standard chemotherapy. After checking eligibility criteria, subjects will be randomized into Fruquintinib plus BSC group (treatment group) or placebo plus BSC group (control group) in a ration of 2:1. Primary Efficacy Endpoint: Overall Survival (OS). Secondary Efficacy Endpoints: Progression free survival (PFS) (According to RECIST Version 1.1), Objective Response Rate (ORR), Disease Control Rate (DCR), . Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.

• Study Type: Interventional
• Enrollment (Actual): 416
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Hutchison Medi Pharma Investigational Site
  • Beijing
    • Beijing, Beijing, China, 100071
      • Hutchison Medi Pharma Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Hutchison Medi Pharma Investigational Site
    • Shenzhen, Guangdong, China, 518036
      • Hutchison Medi Pharma Investigational Site
  • Guangxi
    • Liuzhou, Guangxi, China, 545005
      • Hutchison Medi Pharma Investigational Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Hutchison Medi Pharma Investigational Site
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hutchison Medi Pharma Investigational Site
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Hutchison Medi Pharma Investigational Site
    • Nanjing, Jiangsu, China, 210000
      • Hutchison Medi Pharma Investigational Site
    • Nantong, Jiangsu, China, 226000
      • Hutchison Medi Pharma Investigational Site
    • Xuzhou, Jiangsu, China, 221000
      • Hutchison Medi Pharma Investigational Site
  • Jilin
    • Changchun, Jilin, China, 130000
      • Hutchison Medi Pharma Investigational Site
  • Shandong
    • Qingdao, Shandong, China, 266000
      • Hutchison Medi Pharma Investigational Site
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Hutchison Medi Pharma Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Hutchison Medi Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 and ≤ 75 years of age , with ≥ 40Kg
• Histological or cytological confirmed colorectal cancer
• ECOG performance status of 0-1
• Standard regimen failed or no standard regimen available
• Adequate hepatic, renal, heart, and hematologic functions
• At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
• Signed and dated informed consent
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure

Exclusion Criteria:

• - Pregnant or lactating women
• Any factors that influence the usage of oral administration
• Evidence of CNS metastasis
• Intercurrence with one of the following: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure
• Abuse of alcohol or drugs
• Less than 4 weeks from the last clinical trial - Previous treatment with VEGFR inhibition
• Disability of serious uncontrolled intercurrence infection
• Proteinuria ≥ 2+ (1.0g/24hr)
• Have evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness
• Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc.
• Within 6 months before the first treatment occurs acute myocardial infarction, acute coronary syndrome or CABG
• Bone fracture or wounds that was not cured for a long time
• Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: treatment arm; treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria.	Drug: fruquintinib; fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off; Other Names: HMPL-013
Placebo Comparator: control arm; control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria.	Drug: placebo; fruquintinib placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off; Other Names: HMPL-013 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	every two months after end of treatment (EOT) observation period at 30 days after the last medication	from randomization until death due to any cause, assessed up to 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	Tumor assessment will be performed using radiography method every 8 weeks, until the occurrence of progressive disease (PD), using RECIST v 1.1	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Objective Response Rate (ORR)	Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Disease Control Rate (DCR)	Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1	from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
Safety and tolerance evaluated by incidence, severity and outcomes of AEs	Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 4.0.	from first dose to within 30 days after the last dose

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Collaborators: Fudan University; Eighty-One Hospital of People's Liberation Army
• Investigators: Principal Investigator: Jin Li, PhD, MD, Fudan University

Publications and helpful links

General Publications

• Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018 Jun 26;319(24):2486-2496. doi: 10.1001/jama.2018.7855.
• Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Wang N, Zhang B, Zhang Q, Su W, Guo X, Li J. Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer. Onco Targets Ther. 2021 Aug 11;14:4439-4450. doi: 10.2147/OTT.S307273. eCollection 2021.
• Xu R, Qin S, Guo W, Bai Y, Deng Y, Yang L, Chen Z, Zhong H, Pan H, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Xu J, Chen D, Li W, Sun S, Yu Z, Cao P, Li J, Chen H, Wang J, Wang S, Wang H, Wang N, Zhang B, Han R, Su W, Guo X, Li J. Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial. Future Oncol. 2021 Apr;17(11):1339-1350. doi: 10.2217/fon-2020-0875. Epub 2020 Dec 16.
• Li J, Guo W, Bai Y, Deng Y, Yang L, Chen Z, Zhong H, Xu R, Pan H, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Xu J, Chen D, Li W, Sun S, Yu Z, Cao P, Shen L, Chen H, Wang S, Wang H, Fan S, Guo X, Wang N, Han R, Zhang B, Qin S. Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial. Adv Ther. 2020 Nov;37(11):4585-4598. doi: 10.1007/s12325-020-01477-w. Epub 2020 Sep 8.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 17, 2017

Study Registration Dates

• First Submitted: December 8, 2014
• First Submitted That Met QC Criteria: December 9, 2014
• First Posted (Estimate): December 11, 2014

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: colorectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2013-013-00CH1